Liver Regeneration Associated Protein (ALR) Exhibits Antimetastatic Potential in Hepatocellular Carcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-03

AUTHORS

Rania Dayoub, Hannah Wagner, Frauke Bataille, Oliver Stöltzing, Thilo Spruss, Christa Buechler, Hans-Jürgen Schlitt, Thomas S. Weiss

ABSTRACT

Augmenter of liver regeneration (ALR), which is critically important in liver regeneration and hepatocyte proliferation, is highly expressed in cirrhotic livers and hepatocellular carcinomas (HCC). In the current study, the functional role of ALR in hepatocancerogenesis was analyzed in more detail. HepG2 cells, in which the cytosolic 15 kDa ALR isoform was reexpressed stably, (HepG2-ALR) were used in migration and invasion assays using modified Boyden chambers. Epithelial-mesenchymal transition (EMT) markers were determined in HepG2-ALR cells in vitro and in HepG2-ALR tumors grown in nude mice. ALR protein was quantified in HCC and nontumorous tissues by immunohistochemistry. HepG2-ALR, compared with HepG2 cells, demonstrated reduced cell motility and increased expression of the epithelial cell markers E-cadherin and Zona occludens-1 (ZO-1), whereas SNAIL, a negative regulator of E-cadherin, was diminished. Matrix metalloproteinase MMP1 and MMP3 mRNA expression and activity were reduced. HepG2-ALR cell-derived subcutaneously grown tumors displayed fewer necrotic areas, more epithelial-like cell growth and fewer polymorphisms and atypical mitotic figures than tumors derived from HepG2 cells. Analysis of tumor tissues of 53 patients with HCC demonstrated an inverse correlation of ALR protein with histological angioinvasion and grading. The 15 kDa ALR isoform was found mainly in HCC tissues without histological angioinvasion 0. In summary the present data indicate that cytosolic ALR reduces hepatoma cell migration, augments epithelial growth and, therefore, may act as an antimetastatic and EMT reversing protein. More... »

PAGES

221-228

Identifiers

URI

http://scigraph.springernature.com/pub.10.2119/molmed.2010.00117

DOI

http://dx.doi.org/10.2119/molmed.2010.00117

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1068965295

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21152698


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